The proposed work consists of studies on fundamental aspects of the physiology of spirochetes. Diverse species of spirochetes that can be cultured in vitro will be studied. The physiological characteristics which will be investigated may be common to all spirochetes, or are widespread among these bacteria. Thus, it is expected that findings obtained through the proposed studies will be applicable to pathogenic spirochetes that cannot be cultured in vitro, such as Treponema pallidum and species of Borrelia. The project includes studies on physiological interactions of spirochetes with other microorganisms. This part of the project comprises investigations of spirochetes growing in continuous culture with other bacteria, as well as comparative studies on substrate transport, cell surface to volume ratios, levels of dissimilatory enzymes, and chemotactic responses. Other proposed studies deal with the physiology of spirochetes in viscous environments, specifically with their growth and certain enzymatic activities. Finally, investigations of purine salvage and interconversion in spirochetes, and of amino acid metabolism in these bacteria are planned. The main objective of the proposed research is to increase our limited knowledge of the physiology of spirochetes, a group of bacteria important to humans for the diseases some of them cause, as well as for their widespread participation in a variety of natural processes.